Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Methotrexate (MTX) followed by citrovorum factor (CVF) rescue was evaluated for its effectiveness in reducing graft-versus-host disease (GVHD) in lethally irradiated dogs transplanted with bone marrow from unrelated histoincompatible donors. Animals were given no immunosuppressive therapy (group A) or a combined regimen of MTX and CVF (group AMC). These two groups were compared with a group of animals transplanted earlier given MTX alone (group AM). Ainmals in the AMC group lived significantly longer than the A group (p less than 0.05). Engraftment rate, hematopoietic recovery and incidence of GVHD were similar in all three groups. Incidence of early deaths was significant in the AM group (p less than 0.05). It is concluded that MTX combined with CVF increases survival and is an effective posttransplantation immunosuppressive regimen with minimal toxicity.
 ...
PMID:Methotrexate and citrovorum factor after histoincompatible allogeneic bone marrow transplants in dogs. 3 Feb 47

Ursodiol is a hydrophilic, non-hepatotoxic bile salt indicated for the medical treatment of cholesterol gallstones. This pilot study explored the use of prophylactic ursodiol in an attempt to decrease the incidence and severity of veno-occlusive disease (VOD) of the liver following allogeneic bone marrow transplantation (BMT). Between February 1991 and January 1992, 22 consecutive patients undergoing BMT for hematologic malignancies received the BU(4)/CY(2) preparative regimen and CSA/MTX for GVHD prophylaxis. Ursodiol, 600-900 mg daily by mouth was begun at least 1 day prior to beginning the preparative regimen. Results for this pilot group were compared to a control group of 28 consecutive patients transplanted between June 1989 and January 1991 with the same regimen without ursodiol. There were no significant differences in disease or clinical status between the groups pretransplant. However, mean baseline AST levels were significantly higher in the ursodiol group, 28.0 U/l vs 18.1 U/l in the control group (p = 0.001). The median maximum bilirubin observed post-transplant was 2.35 mg/dl (range 0.9-45) in the ursodiol group, and 5.05 mg/dl (range 0.7-29.4) in controls. The incidence of VOD was 2/22 (9.1%) in the ursodiol group and 18/28 (64.3%) in controls (p = 0.0001). Death due to VOD occurred in 1/22 patients (4.5%) in the ursodiol group and in 6/28 (21.4%) controls (p = 0.12). Our data suggest that ursodiol may decrease the incidence of VOD in allogeneic BMT patients.
 ...
PMID:Pilot trial of prophylactic ursodiol to decrease the incidence of veno-occlusive disease of the liver in allogeneic bone marrow transplant patients. 142 93

Recipients receiving marrow from donors other than HLA identical siblings (alternative donors) treated by monotherapy with either methotrexate (MTX, n = 5) or cyclosporin A (CSA, n = 10) were compared with 28 recipients of alternative donor marrow receiving MTX + CSA. The former group had a cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) of 73% compared with 34% in the latter group (p = 0.009). The incidence of chronic GVHD was 75% and 41% in the two groups respectively, a difference that was not statistically significant. Death caused by GVHD was 47% in recipients of alternative bone marrow treated with monotherapy vs 12% in those treated with MTX + CSA (p = 0.008). The actuarial 4-year patient survival was 7% and 46% in the two groups, respectively (p = 0.04). Compared with HLA identical siblings the recipients of alternative marrow treated with monotherapy had an increased risk of grade II-IV acute GVHD (p less than 0.0001), an increased death rate by GVHD (p = 0.0001) and a decreased survival (p less than 0.0001). When MTX was combined with CSA the recipients of alternative marrow had an increased risk of grade II-IV acute GVHD (p = 0.005), but death by GVHD (12 vs 6%) and 4-year patient survival (46 vs 45%) did not differ.
 ...
PMID:Decreased incidence of graft-versus-host disease and improved survival with methotrexate combined with cyclosporin compared with monotherapy in recipients of bone marrow from donors other than HLA identical siblings. 154 46

A total of 21 multiply transfused patients with severe aplastic anemia (SAA) were treated with bone marrow transplantation between March 1985 and September 1990: 20 allogeneic and one syngeneic transplants. A positive response in mixed lymphocyte culture (MLC) was also noted in 7 allogeneic recipients. Pregraft conditioning included high-dose cyclophosphamide (CY) 200 mg/kg over 4 consecutive days, followed by 300 cGy total-body irradiation the day before BMT. Seventeen patients older than 14 years received additional donor buffy-coat cells infusion for 5 days posttransplant. A combination of methotrexate and cyclosporine was used for prophylaxis of graft-versus-host disease. Seventeen patients were alive with a functional graft, and Kaplan-Meier product limit estimates showed a 80.95% probability of survival at 67.7 months. There were 4 deaths: two died of primary graft failure, one from secondary rejection, and the other from chronic GVHD-related complications. Acute GVHD, grade I was noted in only one patient (5.6%). In contrast, chronic GVHD was observed in 10 out of 18 (55.6%) evaluable patients. Venoocclusive liver disease and interstitial pneumonitis were not diagnosed. Our findings indicate that the combination of CY/TBI/BC is well tolerated and results in a low incidence of graft failure/rejection in multiply transfused Chinese patients who received transplants for SAA. The MTX/CsA combination was confirmed as being remarkable in reducing the incidence and severity of acute GVHD. For patients with SAA under the age of 40, with an HLA-identical sibling, we highly recommend BMT as the treatment of choice.
 ...
PMID:Bone marrow transplantation for severe aplastic anemia--a study of twenty-one Chinese patients in Taiwan. 154 48

The use of cyclosporine-A/methotrexate (CyA/MTX) for graft-versus-host disease (GVHD) prophylaxis is safe and effective for patients undergoing allogeneic bone marrow transplantation after preparation with cyclophosphamide and total body irradiation. We report 87 patients prepared for allogeneic transplant with busulfan 4 mg/kg/d orally for 4 days, followed by cyclophosphamide 60 mg/kg/d intravenously for 2 days (Bu4Cy2). A marked increase in hepatotoxicity was observed in 20 patients administered CyA/MTX, compared with 67 historical control patients who received CyA/methylprednisolone (CyA/MP) for GVHD prophylaxis with all other treatment and support variables remaining constant. The incidence of hyperbilirubinemia (bilirubin greater than or equal to 2 mg/dL) increased from 48% to 80% (P = .02), and the mean maximal bilirubin increased from 4.67 +/- 7.27 to 8.72 +/- 8.73 mg/dL (P = .04), when CyA/MTX was used in place of CyA/MP for GVHD prophylaxis. In addition, the incidence of veno-occlusive disease (VOD) increased from 18% to 70% (P = .0001), and death caused by VOD increased from 4.5% to 25% (P = .02). Survival was not significantly different for the two groups because of a higher non-VOD death rate in patients receiving CyA/MP for GVHD prophylaxis (P = .77). We suggest caution when using Bu4Cy2 in combination with CyA/MTX for GVHD prophylaxis.
 ...
PMID:Marked increase in veno-occlusive disease of the liver associated with methotrexate use for graft-versus-host disease prophylaxis in patients receiving busulfan/cyclophosphamide. 158 25

Allogeneic marrow transplantation from an HLA-identical sibling has proven to be an effective treatment for severe aplastic anemia with restoration of normal hematopoiesis and long-term survival in 70-80% of recipients. Results are related to patient age, with improved survival in younger patients. Marrow transplantation from HLA nonidentical family and unrelated donors has been less successful and is the focus of ongoing clinical research. Graft rejection and graft-versus-host disease (GVHD) remain major problems. A number of pre- and post-transplant immunosuppressive regimens to prevent these complications continue to be studied. The risk of graft rejection is increased in patients who have been transfused before transplant, whereas the risk is decreased with the infusion of larger numbers of transplanted marrow cells. The incidence of graft rejection is 10-32% when cyclophosphamide is used alone as the pretransplant conditioning regimen. The addition of donor buffy coat cells and whole body or limited field radiation have reduced the rate of graft rejection, but increased the incidence of complications such as chronic GVHD and secondary malignancies. GVHD is an immune disorder caused by incompatibility between donor and recipient for histocompatibility antigens. Approximately 18-40% of patients experience moderate to severe acute GVHD. Previous pregnancy in female donors and increasing age of the patient are factors predictive of its development. Methotrexate and cyclosporin have been used most frequently as prophylactic immunosuppressive agents; various combinations of these drugs and prednisone are being evaluated. Symptomatic chronic GVHD occurs in approximately 25% of recipients.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Bone marrow transplantation for severe aplastic anemia. 193 61

The beneficial effect of deoxyspergualin (DSG, NKT-01) on lethal graft-versus-host disease in mice has been studied in a major histoincompatible donor-recipient combination. Suppression of the effector mechanisms responsible for the lethal outcome in this GVHD model is also noted. This study reveals: (1) DSG has a marked potential for treatment of lethal GVHD; (2) DSG and methotrexate in combination yield longer survival times than DSG or MTX alone; (3) long-term survivors, following DSG treatment, become stable chimeras as evidenced by cell-surface analysis of spleen cells; and (4) high activity of H-2-reactive cytotoxic T lymphocytes is detected in spleens of the mice with lethal GVHD, whereas natural killer activity is only slightly increased. DSG inhibits CTL activity not only in the induction stage but also in the advanced stage of the disease. These findings indicate that DSG might be beneficial in clinical bone marrow transplantation either alone or in combination with MTX.
 ...
PMID:Deoxyspergualin in lethal murine graft-versus-host disease. 200 30

An 8-year-old boy with a granulocytic sarcoma of the proximal ileum metastatic to mesenteric lymph nodes was placed into complete remission with surgical excision of the primary tumor and conventional induction chemotherapy with daunorubicin and cytosine arabinoside. He was then treated with high dose cytosine arabinoside, fractionated total body irradiation, and allogeneic marrow transplantation from his 22-month-old brother who was completely matched at the major histocompatibility complex. Methotrexate was given following the transplant to prevent graft-versus-host disease (GVHD). His post-transplantation course was complicated by a transient autoimmune hemolytic anemia related to an ABO blood group incompatibility and hepatic fungal microabscesses which responded to Amphotericin therapy. Four years following the transplant the patient remains in complete remission. The prognosis for patients with granulocytic sarcoma has been poor although, perhaps, improved over the past decade. This is the first published case report of successful treatment of a granulocytic sarcoma of the ileum by allogeneic marrow transplantation.
 ...
PMID:Granulocytic sarcoma of the ileum treated by bone marrow transplantation. 202 76

Intensive chemoradiotherapy conditioning regimens and acute graft-versus-host disease (GVHD) are both associated with significant morbidity and mortality after bone marrow transplantation. In this study, we investigated whether the conditioning regimen affected the development of acute GVHD. Thirty-four patients, four with severe aplastic anemia and 30 with a lymphohemopoietic malignancy, were prepared for transplantation either with cyclophosphamide (CY) alone, with CY combined with total body irradiation (TBI) or CY combined with etoposide and either TBI or busulfan. GVHD prophylaxis included methotrexate (MTX 10 mg/m2) given on days 1, 3 and 6, and daily cyclosporine (CSP) on days--1 through 180. The overall incidence of acute GVHD was 36% (15% for HLA identical, 87% for HLA non-identical recipients). However, when assessed by the severity of conditioning regimen-related toxicity, the incidence of GVHD grades II-IV (HLA identical; HLA non-identical) was 0% (0%; 0%), 37% (20%; 67%) and 50% (22%; 100%) for patients with mild, moderate and severe toxicity, respectively. Compliance with GVHD prophylaxis declined with increasing intensity and toxicity of the conditioning regimen. These data suggest that a regimen of three doses of MTX and daily CSP is as effective as four doses of MTX/CSP for GVHD prophylaxis in patients given HLA identical marrow grafts. However, GVHD regimen compliance and efficacy of GVHD prevention are inversely related to the intensity of the conditioning regimen.
 ...
PMID:Conditioning-related toxicity and acute graft-versus-host disease in patients given methotrexate/cyclosporine prophylaxis. 205 56

Eighteen patients with leukemia have received HLA-identical allogeneic bone marrow transplantation (BMT) at our hospital since 1981. Fifteen of these patients have been living without relapse. for prophylaxis of GVHD, MTX was used in 8 patients, and cyclosporine (CSP) together with MTX in 6 patients, 3 received multiple agents at much smaller dosage, including monoclonal antibody. All patients received intravenous placental gamma-globulin, and 16 received garlic extract. Three patients died. One, who neither received MTX, nor CSP died of hyperacute GVHD, one who did not receive garlic extract died of GMV pneumonia, and the third one died of tuberculosis 18 months after BMT.
 ...
PMID:Allogeneic bone marrow transplantation for the treatment of leukemia. 211 28


1 2 3 4 5 6 7 8 9 10 Next >>